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Genes May Predict Cognitive Decline in Parkinsonís Disease

- Mar 08 2012

People with Parkinson’s disease (PD) who carry a gene variation known as APOE ε4 may have an increased risk of developing dementia, according to research published in the February 16 online edition of the journal Movement Disorders. This gene variation already has been linked to Alzheimer’s, and the study suggests that APOE ε4 might contribute to dementia in both PD and Alzheimer’s.

Mild cognitive impairment — distractibility, forgetfulness, or difficulty with planning — is a common symptom of PD. As many as 80 percent of people with PD develop some level of dementia in old age. Known risk factors for dementia in PD include older age, and PD severity, but the results of previous research attempting to link individual genes to problems with memory or attention, for example, have been inconsistent.

Researchers led by Andrew Siderowf, M.D., M.S., at the University of Pennsylvania, investigated whether variations in two genes associated with dementia in Alzheimer’s disease and other neurodegenerative diseases also influence the course of cognitive decline in PD. These genes are called apolipoprotein E (APOE) and microtubule-associated protein tau (MAPT). For the most part these gene variations do not affect gene function, they are more like alternative ways of spelling a word such as “colour” instead of “color." In addition, the scientists looked for a link to variations in the gene catechol-O-methyltransferase (COMT), which was previously associated with cognitive changes in PD.

The researchers drew blood from 212 study participants with PD and analyzed DNA for these genes. Participants were age 60 and older and had been living with PD for nearly seven years on average. About 70 percent of participants were men. At the time they enrolled in the study, all participants took a standard test of cognitive ability known as the Dementia Rating Scale-2 or DRS-2 for short. In addition, the researchers assessed participants’ motor symptoms. These tests were repeated annually for up to four years.

Results

People who carried any variation in the APOE, MAPT and COMT genes all performed equally well on cognitive tests at their initial evaluation.

Over time, however, scores on the DRS-2 test declined significantly among people who carried a variant in APOE, called APOE ε4.

Carrying a variation in MAPT gene, called MAPT H1/H1, was associated with lower scores on the memory portion of the DRS-2 test throughout the study period, but not with declining scores.

People with the COMT Met/Met gene variation tended to score higher on the portion of the DRS-2 measuring ability to pay attention.

What Does It Mean?

This study links the APOE gene variant APOE ε4 to the development of dementia in PD, and suggests that the risk of dementia is about three times higher for people carrying this variant. This raises the question of genetic testing: would knowing whether they carry the gene help a person with Parkinson’s to make life decisions? For now, the answer is not clear. One shortcoming of the study is that participants were only followed for a few years, so the long-term influence of APOE ε4 on cognition is not known. In addition, even for a gene-carrier, the exact course and timing of disease progression cannot be predicted. Other factors, too, can influence the development of dementia.

Though the results at this point are most valuable to researchers who want to clarify the genetic factors contributing to dementia in PD, this study highlights the progress being made to help identify risk factors that may one day predict changes in cognition for people living with this disease. Future studies that test interventions for better cognitive performance in PD are required. These studies may have to stratify participants by their APOE ε4 genetic status.

Related Resources

If you would like to learn more about cognition and Parkinson's, view PDF's online seminar, "Cognition and PD: What You've Always Wanted to Know but Were Too Afraid to Ask," led by Alexandar Tröster, M.D.